Dry eye syndrome is a common disease with a prevalence rate of 5.5-15% depending on population, age and diagnosis standard (1,2). This disease is characterized by pain, irregular corneal surface, blurred and fluctuating vision, and increased risk of corneal ulcer (3,4). The change in corneal permeability caused by chronic dry eyes and keratitis sicca resulting from unstable tear film has been known to cause inflammations, which has been demonstrated by increased inflammation-mediated chemokine and cytokine in tears, increased immune activity and expression of adhesion molecules (HLA-DR and inter-cellular adhesion molecule 1 [ICAM-1]) by conjunctival epithelial cells, and increased T lymphocytes in the conjunctiva (5,6). Corneal ulcer resulting from keratoconjunctivitis sicca (KCS) may lead to poor vision, vision loss and, even blindness (7,8). The level and activity of matrix metalloproteinase-9 (MMP-9) are reported to increase greatly not only in the tears of patients with dry eye syndrome (9), but also in the corneal epithelium and tears of experimental dry eye (EDE) mice (10).
Recently, it has been consistently reported that inflammation and apoptosis on ocular surface play an important role in the development of dry eye syndrome (11). Hyperosmotic stress and increased inflammatory cytokines (i.e., interleukin (IL)-1, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β) associated with dry eye syndrome have been known to increase the expression of MMP-9 by corneal epithelial cells (12). These chronic inflammatory environments are in part due to the characteristic pathological degeneration of the conjunctival epithelium such as squamous metaplasia and loss of goblet cells (13).
Angiogenesis, a process involving the growth of new blood vessels from pre-existing vessels, is known as a fundamental process in various physiological and pathological conditions including wound healing, embryonic development, chronic inflammation, and tumor development and transition (14,15). Also, angiogenesis is known to be involved in various conditions that may cause loss of vision, such as diabetic retinopathy, macular degeneration, retinopathy of prematurity and retinal vein occlusion (16). New blood vessels are known to grow from pre-existing veins through a series of processes including degradation of the basement membrane (BM) and extracellular matrix (ECM) of endothelial cells by proteases (17,18), proliferation and migration of endothelial cells (19), and formation and occlusion of vascular tubes (20). With regard to vision loss caused by angiogenesis-associated retinal damage, it is known that the suppression of one or more of the above processes is of potential therapeutic value (16).
Sialyllactose (Neu5Ac α-2,3-D-Gal β-1,4-D-Glc) (FIG. 1) is a sialic acid including the glycosphingolipid of GM3 ganglioside, and is commonly found in blood plasma and cell membrane of mammals (12,22). However, there has been no research about the action of sialyllactose on dry eye syndrome or other eye diseases.
Throughout this specification, a number of literatures and patent documents are referenced and cited. The disclosure of the cited literatures and patent documents are incorporated herein by reference to more clearly explain the background art and the present invention.